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High-Throughput Mapping of B Cell Receptor Sequences to Antigen Specificity.
Cell ( IF 45.5 ) Pub Date : 2019-11-28 , DOI: 10.1016/j.cell.2019.11.003
Ian Setliff 1 , Andrea R Shiakolas 2 , Kelsey A Pilewski 2 , Amyn A Murji 2 , Rutendo E Mapengo 3 , Katarzyna Janowska 4 , Simone Richardson 5 , Charissa Oosthuysen 5 , Nagarajan Raju 2 , Larance Ronsard 6 , Masaru Kanekiyo 7 , Juliana S Qin 8 , Kevin J Kramer 2 , Allison R Greenplate 8 , Wyatt J McDonnell 9 , Barney S Graham 7 , Mark Connors 10 , Daniel Lingwood 6 , Priyamvada Acharya 11 , Lynn Morris 12 , Ivelin S Georgiev 13
Affiliation  

B cell receptor (BCR) sequencing is a powerful tool for interrogating immune responses to infection and vaccination, but it provides limited information about the antigen specificity of the sequenced BCRs. Here, we present LIBRA-seq (linking B cell receptor to antigen specificity through sequencing), a technology for high-throughput mapping of paired heavy- and light-chain BCR sequences to their cognate antigen specificities. B cells are mixed with a panel of DNA-barcoded antigens so that both the antigen barcode(s) and BCR sequence are recovered via single-cell next-generation sequencing. Using LIBRA-seq, we mapped the antigen specificity of thousands of B cells from two HIV-infected subjects. The predicted specificities were confirmed for a number of HIV- and influenza-specific antibodies, including known and novel broadly neutralizing antibodies. LIBRA-seq will be an integral tool for antibody discovery and vaccine development efforts against a wide range of antigen targets.

中文翻译:

B细胞受体序列到抗原特异性的高通量映射。

B细胞受体(BCR)测序是用于询问对感染和疫苗接种的免疫反应的强大工具,但它提供了有关测序BCR抗原特异性的有限信息。在这里,我们提出了LIBRA-seq(通过测序将B细胞受体与抗原特异性连接)的技术,该技术可将成对的重链和轻链BCR序列与其关联的抗原特异性进行高通量映射。B细胞与一组DNA条形码的抗原混合,这样抗原条形码和BCR序列均可通过单细胞下一代测序回收。使用LIBRA-seq,我们绘制了来自两个HIV感染者的数千个B细胞的抗原特异性。确认了多种HIV和流感特异性抗体的预测特异性,包括已知和新颖的广泛中和抗体。LIBRA-seq将成为针对广泛抗原靶标的抗体发现和疫苗开发工作的不可或缺的工具。
更新日期:2019-11-29
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